The pathogenesis of lipid storage diseases is under investigation using a variety of approaches. The pathogenesis of phytanic acid storage disease is being explored by examining the effects of phytanic acid on growth and metabolism of human fibroblasts in cell culture and of glioma cells in culture. The influence of phytanate incorporation on membrane transport and membrane structure will be examined; the possible effects of phytanate on rates and patterns of phospholipid biosynthesis will be studied. The incorporation of phytanic acid into phospholipids will be studied with regard to positional specificity and rates relative to incorporation of straight-chain fatty acids. The significance of the accumulation of bis-(monoacylglyceroyl) phosphate (bis-(MAG)P) in tissues of patients with Niemann-Pick disease and related disorders will be considered. The origins of bis-(MAG)P and its further metabolism will be studied using tracer techniques. Since 4,4'- diethylaminoethoxyhexestrol has been reported to cause accumulation of bis-(MAG)P, it will be used as a tool to examine the biosynthesis and degradation of this compound. The central question in relation to human disease is the extent to which the accumulation of bis-(MAG)P contributes to pathogenesis. Several cases have been reported in which there is accumulation of bis-(MAG)P without accumulation of sphingomyelin. This raises question as to the primary import of sphingomyelin accumulation in some variants of Niemann-Pick disease.